Abstract 329TiP
Background
T-DM1, a HER2-targeted antibody–drug conjugate, and atezolizumab, a PD-L1-targeted monoclonal antibody, have shown clinical benefit in HER2-positive and triple-negative breast cancer (BC), respectively. In addition to its cytotoxic effects, T-DM1 potentiates antitumor immunity with a synergistic effect observed in preclinical models when combining PD-L1 and HER2 inhibitors. Exploratory analyses of the randomized, phase 2 KATE2 study suggested a progression free survival (PFS) and overall survival (OS) benefit with atezolizumab plus T-DM1 compared to T-DM1 alone in pre-treated patients with HER2-positive and PD-L1-positive locally advanced (LA)/metastatic (M)BC. These data support further study of T-DM1 plus atezolizumab in this patient population.
Trial design
KATE3 (NCT04740918) is an ongoing randomized, multicenter, double-blind, Phase 3 study of T-DM1 with atezolizumab or placebo in trastuzumab- (± pertuzumab) and taxane-pretreated LA/MBC with centrally-determined HER2-positive and PD-L1–positive (assessed ≤6 months before study entry) unresectable LA/MBC. Patients must have received ≤2 prior lines of therapy for MBC and experienced disease progression during or after LA/MBC therapy or during or within 6 months after (neo)adjuvant therapy. Previous adjuvant T-DM1 is allowed if disease recurrence occurred >6 months after completing T-DM1 treatment. Previous treatment with CD137 agonists and PD-(L)1–targeted agents is allowed. Patients are randomized 1:1 to 3-weekly cycles of T-DM1 3.6 mg/kg and atezolizumab 1200 mg or T-DM1 3.6 mg/kg and placebo. Randomization is stratified by hormone receptor status, disease status, and world region. The multiple primary endpoints are investigator-assessed PFS and OS. Secondary endpoints include objective response rate, response duration, PFS assessed by a blinded independent central review committee, PFS and OS in those with brain metastases at baseline, central nervous system PFS, patient-reported outcomes, and safety. Approximately 350 patients will be enrolled at approximately 175 sites worldwide.
Clinical trial identification
NCT04740918.
Editorial acknowledgement
Medical writing support was provided by Tracy McNally, PhD, and Holly Strausbaugh, PhD, on behalf of Twist Medical, LLC, and funded by F. Hoffmann-La Roche, Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche, Ltd.
Funding
F. Hoffmann-La Roche, Ltd.
Disclosure
S. Loi: Financial Interests, Institutional, Expert Testimony, Consultant: Aduro Biotech; Financial Interests, Institutional, Advisory Board, Consultant: Novartis; Financial Interests, Institutional, Advisory Board, Consultant: GlaxoSmithKline; Financial Interests, Institutional, Advisory Board, Consultant: Roche Genentech; Financial Interests, Institutional, Advisory Board, Consultant: AstraZeneca; Financial Interests, Institutional, Advisory Board, Consultant: Silverback Therapeutics; Financial Interests, Institutional, Advisory Board, Consultant: G1 Therapeutics; Financial Interests, Institutional, Expert Testimony, COnsultant: PUMA Biotechnologies; Financial Interests, Institutional, Expert Testimony, Consultant: Pfizer; Financial Interests, Institutional, Expert Testimony, Consultant: Seattle Genetics; Financial Interests, Institutional, Expert Testimony, COnsultant: BMS; Financial Interests, Institutional, Funding, Research: Novartis; Financial Interests, Institutional, Funding, Research: BMS; Financial Interests, Institutional, Funding, Research: Merck; Financial Interests, Institutional, Funding, Research: PUMA Biotechnology; Financial Interests, Institutional, Funding, Research: Eli Lilly; Financial Interests, Institutional, Funding, Research: Nektar Therapeutics; Financial Interests, Institutional, Funding, Research: AstraZeneca; Financial Interests, Institutional, Funding, Research: Seattle Genetics; Financial Interests, Institutional, Funding, Research: Roche - Genentech; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Seattle Genetics; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Novartis; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Bristol Myers Squibb; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Merck; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): AstraZeneca; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Roche Genentech. A. Schneeweiss: Financial Interests, Institutional, Research Grant: Celgene; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Personal, Expert Testimony: Roche; Financial Interests, Personal, Expert Testimony: AstraZeneca; Financial Interests, Personal, Other, Travel expenses: Celgene; Financial Interests, Personal, Other, Travel expenses: Roche; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Celgene; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Tesaro; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Travel expenses: Pfizer; Non-Financial Interests, Personal, Other, Medical writing: Roche; Financial Interests, Personal, Other, Honoraria: Seagen. M. De Laurentiis: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Other, Steering Committee Member: Roche; Financial Interests, Personal, Other, Steering Committee Member: Novartis Amgen; Financial Interests, Personal, Invited Speaker: Novartis Amgen; Financial Interests, Personal, Advisory Board: Novartis Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Writing Engagements: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Other, Steering Committee Member: Pfizer; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Exact Science (Genomic Health); Financial Interests, Personal, Other, Consultant: Seagen; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Writing Engagements: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Sandoz. Y. Li: Financial Interests, Personal, Full or part-time Employment: F. Hoffman-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffman-La Roche Ltd. C. Wiese: Financial Interests, Personal, Full or part-time Employment: Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: Hoffmann-La Roche Ltd. R. Poppe: Financial Interests, Personal, Full or part-time Employment: Roche. L.A. Emens: Financial Interests, Personal, Leadership Role, co-chair of the IMpassion130 study steering committee: Roche; Financial Interests, Personal, Leadership Role, co-chair of the KATE3 study steering committee: Roche; Financial Interests, Personal, Leadership Role, chair of the KATE2 study steering committee: Roche; Financial Interests, Personal, Other, honoraria: AbbVie; Financial Interests, Personal, Other, honoraria: Amgen; Financial Interests, Personal, Other, honoraria: Celgene; Financial Interests, Personal, Other, honoraria: Chugai; Financial Interests, Personal, Other, honoraria: GCPR; Financial Interests, Personal, Other, honoraria: Gilead; Financial Interests, Personal, Other, honoraria: Gritstone; Financial Interests, Personal, Other, honoraria: MedImmune; Financial Interests, Personal, Other, honoraria: Peregrine; Financial Interests, Personal, Other, honoraria: Shionogi; Financial Interests, Personal, Other, honoraria: Syndax; Financial Interests, Personal, Other, honoraria, travel support: AstraZeneca; Financial Interests, Personal, Other, honoraria, travel support: Bayer; Financial Interests, Personal, Other, honoraria, travel support: MacroGenics; Financial Interests, Personal, Other, honoraria, travel support: Replimune; Financial Interests, Personal, Other, honoraria, travel support: Vaccinex; Financial Interests, Personal, Other, travel support: Bristol Myers Squibb; Financial Interests, Personal, Other, travel support: Genentech/Roche; Financial Interests, Personal, Other, travel support: Novartis; Financial Interests, Personal, Stocks/Shares, potential future stock: Molecuvax; Financial Interests, Institutional, Funding: Abbvie; Financial Interests, Institutional, Funding: Aduro Biotech; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Breast Cancer Research Foundation; Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Bolt Therapeutics; Financial Interests, Institutional, Funding: Compugen; Financial Interests, Institutional, Funding: Corvus; Financial Interests, Institutional, Funding: CytomX; Financial Interests, Institutional, Funding: US Department of Defense; Financial Interests, Institutional, Funding: EMD Serono; Financial Interests, Institutional, Funding: Genentech; Financial Interests, Institutional, Funding: Maxcyte; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: National Cancer Institute; Financial Interests, Institutional, Funding: NSABP Foundation; Financial Interests, Institutional, Funding: SU2C; Financial Interests, Institutional, Funding: Silverback; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Translational Breast Cancer Research Consortium; Financial Interests, Institutional, Funding: Takeda; Financial Interests, Institutional, Funding: Tempest; Financial Interests, Institutional, Funding: HeritX; Financial Interests, Personal, Royalties: Aduro Biotech; Financial Interests, Personal, Leadership Role, current Vice President: Society for the Immunotherapy of Cancer (SITC). All other authors have declared no conflicts of interest.